期刊
AIDS RESEARCH AND HUMAN RETROVIRUSES
卷 30, 期 7, 页码 654-664出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/aid.2014.0004
关键词
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资金
- Creative and Novel Ideas in HIV Research Program (CNIHR) [P30 A1027763]
- Office of AIDS Research
- National Institutes of Allergies and Infectious Diseases (NIAID)
- International AIDS Society
- National Center for Research Resources [2G12RR003061-26]
- National Institute on Minority Health and Health Disparities [8G12MD7601-27]
- NIAID of the NIH
- Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19-AI067854-07]
- NIAID [RO1 AI087145, K24AI069994]
- UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]
- CFAR Network of Integrated Systems [R24 AI067039]
- Grants-in-Aid for Scientific Research [25460592] Funding Source: KAKEN
- MRC [MR/K012037/1] Funding Source: UKRI
- Medical Research Council [MR/K012037/1] Funding Source: researchfish
Galectin-9 (Gal-9) is a beta-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-alpha, and IL-1 beta. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r = 0.29; p = 0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3 pg/ml) and in elite controllers (263.3 pg/ml) compared to age-matched HIV-uninfected controls (54 pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.
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